The dendritic cells adopt an ingenious approach here - they not only produce special substances with a cell-damaging effect, they also manage to fight the tumour without the help of T and B cells and natural killer (NK) cells. This complex interaction was discovered by scientists participating in a doctoral programme of the Austrian Science Fund FWF. It was also recently published and commented on in the Journal of Clinical Investigation.
For 15 years now the drug Imiquimod has been authorised for the treatment of certain skin diseases, including some types of skin cancer. And during that period, the drug, which is administered as a skin cream, has proven to be an effective treatment. Despite this therapeutic success, the drug´s exact mechanism of action was not known to date. However, a research group working with Prof. Maria Sibilia, Head of the Institute for Cancer Research at the Medical University of Vienna, has now succeeded in determining some unknown and surprising effects of Imiquimod (Imi) on special immune cells.CELLULAR INFANTRY
The group actually succeeded in demonstrating that CCL2 then causes the migration of additional immune system cells. The analysis of the subsequent activity of these immune cells generated a real surprise for the scientists: the immune cells, called plasmacytoid dendritic cells (pDCs), were considered to be modulators up to now. However, in their reaction to Imi, they proved to be bona fide aggressors.FIGHTING STRATEGY
Overall, the team from the doctoral programme "Inflammation and Immunity" succeeded in discovering a new mechanism of action of dendritic cells in fighting tumours; it had never been possible before to observe such a direct attack on tumours by pDCs. Further studies will reveal the extent to which this discovery will benefit the development of innovative cancer therapies. Some important questions remain open, however, as Dr. Drobits explains: "It is known that some tumour cells produce CCL2 themselves. In other words, they should have triggered the same cascade as Imi. But this did not always result in a positive disease progression. We do not yet know why this is the case and it needs to be explained." In meeting challenges like this, the FWF´s doctoral programme once again proves that it is fulfilling an important goal: to give young scientists the opportunity to work at the vanguard of cutting-edge science.
Original publication: Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells. B. Drobits, M. Holcmann, N. Amberg, M. Swiecki, R. Grundtner, M. Hammer, M. Colonna, and M. Sibilia. J Clin Invest. 2012;122(2):575 585. doi:10.1172/JCI61034.Picture and text available from Monday, March 26 2012, 9 am CET at:
Stefan Bernhardt | PR&D
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
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